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OHSU Study:Rate of Brain Volume Loss Predicts Dementia

04/28/04 Portland, Ore.

Discovery could help doctors plan treatment, prevention before symptoms appear

The rate of brain volume loss may help doctors predict whether a patient will develop dementia before they even start showing signs of the disease, Oregon Health & Science University researchers discovered.

Scientists at the Layton Center for Aging & Alzheimer's Disease Research in the OHSU School of Medicine's Department of Neurology found that rates of total brain volume loss may help identify patients with mild cognitive impairment who are at high risk of developing dementia. The discovery could help doctors plan early treatment strategies and prevention studies.

Joseph F. Quinn, M.D., study co-author and assistant professor of neurology, and cell and developmental biology, OHSU School of Medicine, called the findings "very important."

"The measurements can be used to both screen people for prevention studies and to monitor the effects of intervention," said Quinn, an investigator at the OHSU Layton Center for Aging & Alzheimer's Disease Research.

The study was presented yesterday at the 56th annual meeting of the American Academy of Neurology in San Francisco.

Researchers followed 55 people over the course of 14 years, examining each person twice a year. None of the subjects were cognitively impaired at the start of the study. Tests were conducted to determine cognitive ratings for each individual and their placement in one of three categories: intact cognition, mild cognitive impairment that was stable, and mild cognitive impairment that progressed to Alzheimer's disease.

Eighteen participants did not develop cognitive impairment, while 37 individuals met the criteria for mild cognitive impairment, and 13 of them remained stable. The remaining 24 people declined to Alzheimer's disease. Two brain scans using magnetic resonance imaging, or MRI, were performed on the participants to measure their brain volumes and rates of brain atrophy, or shrinkage.

Researchers found the rate of total brain volume loss was "significantly" different between the three groups. Mildly cognitively impaired individuals who progressed to dementia had a greater rate of atrophy than the cognitively intact group, while the stable impairment group had an intermediate rate of total volume loss.

The volume of the hippocampus, the part of the brain that controls learning and memory, in the impaired group that progressed to dementia was smaller than that of the stable impaired subjects.

Hippocampus volume predicted which mildly cognitively impaired individuals would stay stable and which would decline to Alzheimer's disease with 70 percent accuracy, while the rate of brain volume loss was 62 percent accurate in predicting cognitive outcome. Combining both variables produced the strongest model: 75 percent accuracy.

Scientists have known for several years that people with mild cognitive impairment have some brain atrophy, but until now they haven't known the impact of the rate or total amount of this shrinkage, prior to symptoms, on determining whether, or when, a person develops dementia later in life.

"The longer-term outcome, such as progression to dementia with regard to these differences, has not been studied until very recently, such as in this study," said co-author Jeffrey A. Kaye, M.D., OHSU professor of neurology and director of the Layton Center for Aging & Alzheimer's Disease Research.

Layton Center scientists have long studied a variety of early preventions and treatments to stave off dementia symptoms, but the brain volume study will help them fine-tune each patient's therapy program.

"Strategies under study for the prevention of dementia include prescription drugs like Aricept, supplements like vitamin E and ginkgo biloba, non-steroidal anti-inflammatory agents and cholesterol-lowering 'statin' drugs," Quinn said.

"However, we do not routinely recommend that people take these agents for prevention until we know more facts, since some of them, such as the non-steroidal anti-inflammatory drugs and statins, have significant side effects. Nutritional interventions, physical exercise and mental exercise are also rational and may be studied in the future."

Dementia afflicts 10 percent to 16 percent of people older than 75 and half of the 85-and-older population. Early diagnosis is important so doctors can identify treatable causes of dementia, effectively manage the dementia and related illnesses, and offer support services to the patient and family.